Key Facts

Oesophageal cancer is a highly aggressive malignancy with poor prognosis. The epidemiological shift from squamous cell carcinoma to adenocarcinoma in Western countries parallels the rise in GORD and obesity.

Epidemiology

Approximately 9,300 new cases per year in the UK. The UK has one of the highest incidence rates of oesophageal adenocarcinoma worldwide. Male:female ratio is 2:1 (higher for adenocarcinoma — up to 7:1). Peak incidence is 60-80 years. 5-year survival is approximately 15% overall; ~40-50% for those undergoing curative resection.

Aetiology

Adenocarcinoma (distal/GOJ):

• Barrett oesophagus (30-60x risk)
• Chronic GORD
• Central obesity
• Smoking
• Male sex, Caucasian

Squamous cell carcinoma (mid-oesophagus):

• Smoking (5x risk) + alcohol (5x risk) — synergistic (25x combined)
• Achalasia
• Plummer-Vinson syndrome (iron deficiency + oesophageal web)
• Caustic stricture
• Tylosis (genetic — very high risk)
• HPV (types 16/18)
• Hot beverages (some evidence)

Pathophysiology

Adenocarcinoma arises through the metaplasia-dysplasia-carcinoma sequence in Barrett oesophagus, driven by chronic acid/bile exposure. Key molecular events include TP53 mutation, CDKN2A loss, and HER2 amplification (targetable with trastuzumab). SCC develops from squamous epithelium via dysplasia, driven by carcinogen exposure (tobacco, alcohol metabolites). Both types spread locally (mediastinal invasion), lymphatically (extensive submucosal lymphatic network), and haematogenously (liver, lungs, bone).

Typical Presentation

• Progressive dysphagia: initially solids, then liquids (>70% at presentation)
• Weight loss: often significant (>10% body weight)
• Odynophagia: painful swallowing
• Retrosternal discomfort/pain
• Regurgitation of undigested food

Late Features

• Hoarseness (recurrent laryngeal nerve invasion)
• Chronic cough (tracheo-oesophageal fistula)
• Cervical lymphadenopathy (Virchow's node — left supraclavicular)
• Hepatomegaly (liver metastases)
• Bone pain (skeletal metastases)

Red Flags

• Any progressive dysphagia (urgent OGD regardless of age)
• Dyspepsia with weight loss, anaemia, or vomiting in ≥55 years
• New dysphagia in known Barrett oesophagus
• Aspiration pneumonia (tracheo-oesophageal fistula)

Bedside

• OGD + biopsy: diagnostic — visualise tumour, obtain histology, assess location and length
• Nutritional assessment: weight loss, BMI, albumin

Bloods

• FBC: iron deficiency anaemia
• LFTs: liver metastases
• Albumin: nutritional status
• U&Es, clotting: pre-operative baseline
• HER2 status: on biopsy (adenocarcinoma — if positive, trastuzumab eligible)
• PD-L1 (CPS): immunotherapy eligibility

Imaging

• CT thorax/abdomen/pelvis with contrast: initial staging — local extent, lymphadenopathy, distant metastases
• PET-CT: detects occult metastases, changes management in ~15-20%
• Endoscopic ultrasound (EUS): T and N staging — most accurate for local invasion depth and regional nodes
• Staging laparoscopy: for GOJ/Siewert type II-III tumours to exclude peritoneal disease

Special Tests

• Barium swallow: if OGD not possible; shows shouldering, irregular narrowing
• Bronchoscopy: if tracheo-oesophageal fistula or airway invasion suspected
• Molecular testing: HER2, PD-L1 CPS, MSI status — guide systemic therapy

Non-pharmacological

• MDT discussion: all cases — upper GI cancer MDT (surgeon, oncologist, radiologist, pathologist, CNS, dietitian)
• Nutritional support: dietitian assessment; consider NG tube, PEG/RIG, or parenteral nutrition
• Smoking/alcohol cessation
• Pre-habilitation: exercise and nutrition optimisation before surgery

Pharmacological

• Neoadjuvant chemotherapy (adenocarcinoma):
  • FLOT regimen (5-FU, leucovorin, oxaliplatin, docetaxel): 4 cycles pre-op + 4 cycles post-op — current standard (FLOT4 trial)
  • OR ECF/ECX/EOF/EOX (MAGIC trial — perioperative chemotherapy)
• Neoadjuvant chemoradiotherapy (SCC preferred): carboplatin/paclitaxel + 41.4 Gy (CROSS trial — improved median survival from 24 to 49 months)
• Palliative chemotherapy: FOLFOX, capecitabine/oxaliplatin; median survival ~10 months
• Trastuzumab: add to chemotherapy if HER2-positive adenocarcinoma (ToGA trial)
• Nivolumab/pembrolizumab: checkpoint inhibitors for PD-L1 positive or MSI-high; adjuvant nivolumab post-neoadjuvant chemoRT (CheckMate 577)

Surgical/Interventional

• Oesophagectomy: curative intent for T1-T3 N0-N2 M0 (after neoadjuvant therapy)
  • Ivor Lewis (right thoracotomy + laparotomy): most common for distal/GOJ
  • McKeown (3-stage): for mid/upper oesophageal tumours
  • Minimally invasive (MIO): laparoscopic/thoracoscopic — reduced morbidity
• Endoscopic resection: EMR/ESD for T1a (mucosal) tumours; curative if clear margins and no poor prognostic features
• Oesophageal stenting (SEMS): palliative for dysphagia in inoperable disease
• Palliative radiotherapy: for dysphagia, bleeding, pain

Referral Criteria

• Urgent 2-week wait OGD for dysphagia or alarm symptoms (NICE NG12)
• All confirmed oesophageal cancers to upper GI cancer MDT
• Specialist oesophagogastric cancer centre for surgery (centralised services)

Overall 5-year survival is approximately 15%. Stage-dependent: Stage I ~60-80%, Stage II ~30-40%, Stage III ~15-25%, Stage IV <5%. Neoadjuvant chemo(radio)therapy + surgery gives best outcomes for locally advanced disease. The CROSS trial showed 49-month median survival with neoadjuvant chemoRT vs 24 months with surgery alone for SCC. Complete pathological response to neoadjuvant therapy occurs in ~15-30% and is associated with improved survival. Palliative treatment provides median survival of 6-12 months.

TNM Staging Summary (8th Edition)

Siewert Classification (GOJ Tumours)

Key Trials